CD44 is a non-kinase transmembrane glycoprotein that is overexpressed in cancer stem cells and various cancer types. It binds to hyaluronic acid (HA), which activates CD44 and triggers signaling pathways that promote cell proliferation, survival, and motility. CD44 has multiple isoforms, including CD44s and CD44v, which have distinct functional roles. CD44v can interact with growth factors and cytokines, acting as a coreceptor to facilitate signaling. CD44v is expressed in metastatic tumors and is involved in epithelial-to-mesenchymal transition (EMT) and cancer cell plasticity. CD44 is a potential therapeutic target for cancer, as it is involved in tumorigenesis, stemness, and resistance to chemotherapy. Therapeutic strategies targeting CD44 include antibodies, shRNAs, ectodomain mimics, and aptamers. CD44's role in cancer progression is complex, with different isoforms playing distinct roles in tumor growth, metastasis, and response to therapy. CD44 is regulated by various factors, including transcription factors, epigenetic mechanisms, and miRNAs. CD44 activation influences multiple signaling pathways, including protein kinases, cytoskeletal changes, and transcriptional factors, contributing to cancer cell proliferation, invasion, and angiogenesis. CD44 also modulates metabolic pathways, such as glycolysis, which is critical for cancer cell survival. Understanding CD44's role in cancer is essential for developing targeted therapies.CD44 is a non-kinase transmembrane glycoprotein that is overexpressed in cancer stem cells and various cancer types. It binds to hyaluronic acid (HA), which activates CD44 and triggers signaling pathways that promote cell proliferation, survival, and motility. CD44 has multiple isoforms, including CD44s and CD44v, which have distinct functional roles. CD44v can interact with growth factors and cytokines, acting as a coreceptor to facilitate signaling. CD44v is expressed in metastatic tumors and is involved in epithelial-to-mesenchymal transition (EMT) and cancer cell plasticity. CD44 is a potential therapeutic target for cancer, as it is involved in tumorigenesis, stemness, and resistance to chemotherapy. Therapeutic strategies targeting CD44 include antibodies, shRNAs, ectodomain mimics, and aptamers. CD44's role in cancer progression is complex, with different isoforms playing distinct roles in tumor growth, metastasis, and response to therapy. CD44 is regulated by various factors, including transcription factors, epigenetic mechanisms, and miRNAs. CD44 activation influences multiple signaling pathways, including protein kinases, cytoskeletal changes, and transcriptional factors, contributing to cancer cell proliferation, invasion, and angiogenesis. CD44 also modulates metabolic pathways, such as glycolysis, which is critical for cancer cell survival. Understanding CD44's role in cancer is essential for developing targeted therapies.